氧化应激在醛固酮/盐慢性灌注致肾损害中的作用

Role of oxidative stress in aldosterone/salt chronic infusion-induced renal injury

目的:探讨氧化应激在醛固酮诱导肾损害中的作用。方法:SD大鼠随机分为单纯氯化钠组、醛固酮/盐慢性灌注组、eplerenone组、Tempol组。采用RT-PCR法检测肾皮质NA(D P)H氧化酶亚基p22phox和Nox-4 mRNA水平。结果:醛固酮/盐慢性灌注组大鼠的血压(165±5)mmHg,24 h尿蛋白排泄率(101±24)mg/d,肾皮质脂类过氧化反应产物TBARS水平(0.23±0.02)nmol/mg,与单纯氯化钠组大鼠的(118±3)mmHg、(9±3)mg/d及(0.09±0.01)nmol/mg比较,明显升高(P<0.05);肾皮质NAD(P)H氧化酶亚基p22phox和Nox-4 mRNA表达分别升高(2.8±0.2)倍和(3.9±0.8)倍(P<0.05)。eplerenone或Tempol明显降低了醛固酮/盐灌注组大鼠的血压,分别降低至(127±2)和(125±5)mmHg,尿蛋白排泄率分别降低至(10±2)和(10±3)mg/d,肾皮质TBARS水平分别降低至(0.08±0.01)和(0.11±0.01)nmol/mg(P<0.05)。结论:氧化应激在醛固酮诱导的肾损害中发挥重要作用。

Objective： To explore the role of oxidative stress in the pathogenesis of aldosterone-induced renal injury. Methods： Male Sprague-Dawley rots were randomly divided into 4 groups： NaCl group, aldosterone/salt chronic infusion group, eplerenone group, and Tempol group. The expressions of p22-phox and Nox-4 mRNA in the renal cortex were determined by real-time polymerase chain reaction （RT- PCR）. Results： Compared with NaCl group, the blood pressure, 24-hour proteinuria, and thiobarbituric acid-reactive substances （TBARS） level in renal cortex in aldosterone/salt chronic infusion group were significantly higher （165±5 vs. 118±3 mmHg, 101±24 vs. 9±3 mg/d, and 0.23±0.02 vs. 0.09±0.01 nmol/mg, respectively; all P 〈 0.05）, and the expressions of p22phox and Nox-4 mRNA increased 2.8±0.2 and 3.9±0.8 times,respectively （both P 〈 0.05）. The blood pressure, 24-hour proteinuria, and TBARS level were decreased to 127±2 mmHg, 10±2 mg/d, and 0.08±0.01 nmol/mg in eplerenone group and 125±5 mmHg, 10±3 mg/d, and 0.11±0.01 nmol/mg in Tempol group （all P〈 0.05）. Conclusion： The oxidative stress plays an important role in the progression of aldosterone/salt chronic infusion-induced renal injury.